Membrane trafficking in neuronal maintenance and degeneration.
Membrane trafficking in neuronal maintenance and degeneration.
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DOI：
10.1007/s00018-012-1201-4
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发表时间：
2013-08
影响因子：
8
通讯作者：
Hiesinger, P. Robin
中科院分区：
文献类型：
--
作者：
Wang, Dong;Chan, Chih-Chiang;Cherry, Smita;Hiesinger, P. Robin
膜运输和降解的缺陷是大多数，也许是所有神经退行性疾病的标志。此类缺陷通常导致由于异常内体分选、溶酶体降解或自噬而导致的未降解蛋白质的积累。特定疾病的遗传或环境原因可能直接影响这些膜运输过程。或者，细胞内分选和降解的变化可以作为退化神经元对不相关的原发性缺陷如不溶性蛋白质聚集体或其他神经毒性损伤的细胞反应而发生。重要的是，改变的膜运输可能有助于发病机制或确实保护神经元。因此，观察到膜运输的显著变化伴随着区分病理性改变和保护性改变的挑战性需求。在这里，我们将回顾我们目前关于膜运输在神经元维持和变性中的保护性和破坏性作用的知识。特别是，我们将首先关注什么类型的膜运输保持健康的神经元存活的问题。接下来，我们将讨论已知在阿尔茨海默病和其他tau蛋白病、帕金森病、polyQ疾病、周围神经病和溶酶体贮积症中发生的膜运输的改变。结合维护和退化的观点，可以深入了解如何区分膜运输功能时，保护或有助于退化。
Defects in membrane trafficking and degradation are hallmarks of most, and maybe all, neurodegenerative disorders. Such defects typically result in the accumulation of undegraded proteins due to aberrant endosomal sorting, lysosomal degradation, or autophagy. The genetic or environmental cause of a specific disease may directly affect these membrane trafficking processes. Alternatively, changes in intracellular sorting and degradation can occur as cellular responses of degenerating neurons to unrelated primary defects such as insoluble protein aggregates or other neurotoxic insults. Importantly, altered membrane trafficking may contribute to the pathogenesis or indeed protect the neuron. The observation of dramatic changes to membrane trafficking thus comes with the challenging need to distinguish pathological from protective alterations. Here, we will review our current knowledge about the protective and destructive roles of membrane trafficking in neuronal maintenance and degeneration. In particular, we will first focus on the question of what type of membrane trafficking keeps healthy neurons alive in the first place. Next, we will discuss what alterations of membrane trafficking are known to occur in Alzheimer’s disease and other tauopathies, Parkinson’s disease, polyQ diseases, peripheral neuropathies, and lysosomal storage disorders. Combining the maintenance and degeneration viewpoints may yield insight into how to distinguish when membrane trafficking functions protectively or contributes to degeneration.
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